Publications by authors named "Zhengwei Fu"

224 Publications

Propamocarb exposure has the potential to accelerate the formation of atherosclerosis in both WT and ApoE mice accompanied by gut microbiota dysbiosis.

Sci Total Environ 2021 Aug 12;800:149602. Epub 2021 Aug 12.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, Zhejiang, China. Electronic address:

Propamocarb is a systemic carbamate fungicide used to fight diseases. The effect of propamocarb on the formation of atherosclerosis was evaluated in wild-type (WT) and ApoE knockout (ApoE) mice. C57BL/6 J WT mice were fed control diet or high-fat diet (HFD) with 20 mg/L propamocarb in drinking water for 24 weeks. Propamocarb significantly increased the serum levels of triglyceride, cholesterol and low-density lipoprotein cholesterol while decreasing high-density lipoprotein cholesterol. Simultaneously, propamocarb facilitated lipid accumulation in the liver and increased the expression of cholesterol synthesis and transport genes in the liver and ileum. Lipid accumulation was observed in the aortic roots of the propamocarb-treated mice fed HFD, and similar results were also observed with whole aorta staining. In addition, propamocarb exposure significantly increased the mRNA levels of IL-1β, TNF-α, ICAM-1, and VCAM-1 in the aorta and the serum IL-1β, IL-6, and TNF-α levels in HFD groups treated with propamocarb. In ApoE mice, the results were consistent with those obtained in WT mice after exposure to 20 mg/L propamocarb for 10 weeks. Meanwhile, propamocarb significantly increased the levels of CD36, NF-κB, VCAM-1 and ICAM-1 proteins in the aortas of ApoE mice. Propamocarb further disrupted cholesterol metabolism and enhanced atherosclerosis and inflammatory responses much more substantially, indicating that propamocarb has the potential to accelerate the formation of atherosclerosis. An analysis of gut microbiota revealed that propamocarb altered the composition of gut microbiota in both WT and ApoE mice. Interestingly, propamocarb increased the abundance of Peptostreptococcaceae, Ruminococcaceae, and Clostridiales_VadinBB60_group, which are related to atherosclerosis at the family level. The abundance of Paeniclostridium, Allobaculum, and Clostridioides, which are closely related to atherosclerosis, was also increased by propamocarb exposure. Our findings indicate that propamocarb exposure may promote atherosclerosis by disrupting lipid metabolism, increasing the inflammatory response, and altering the structure of gut microbiota.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149602DOI Listing
August 2021

Exposure to hexafluoropropylene oxide dimer acid (HFPO-DA) disturbs the gut barrier function and gut microbiota in mice.

Environ Pollut 2021 Aug 9;290:117934. Epub 2021 Aug 9.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, China. Electronic address:

Hexafluoropropylene oxide dimer acid (HFPO-DA) is the substitute for perfluoro octanoic acid (PFOA), and recently it has been detected in environmental water samples worldwide and has multiple toxicities. However, whether it will affect the intestines and gut microbiota remains unclear. In this study, in order to evaluate the gut toxicity of HFPO-DA in mammals, male mice were orally exposed to 0, 2, 20, 200 μg/L HFPO-DA, respectively, for 6 weeks. Our results showed that HFPO-DA exposure caused colonic inflammation which was coupled with increased TNF-α levels in serum and increased mRNA expression levels of TNF-α, p65, TLR4, MCP-1 of the colon in mice after exposure to 200 μg/L HFPO-DA. We also found that HFPO-DA exposure induced the decreased mRNA expression levels and protein levels of MUC2 and ZO-1, which means the dysfunction of gut barrier in the colon. In the ileum, we found that HFPO-DA exposure induced the increased mRNA expression levels of various inflammatory factors, but no obvious changes was found to barrier function. Additionally, HFPO-DA exposure caused the imbalance of cecal gut microbiota and changes of cecal microbiota diversity. Taken together, all these results indicate the potential gut toxicity of HFPO-DA and is perceived as a major problem of health risk that affects the inflammation, gut barrier dysfunction, and gut microbiota disturbance in mammals.
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http://dx.doi.org/10.1016/j.envpol.2021.117934DOI Listing
August 2021

Hydrolyzed Chicken Meat Extract Attenuates Neuroinflammation and Cognitive Impairment in Middle-Aged Mouse by Regulating M1/M2 Microglial Polarization.

J Agric Food Chem 2021 Sep 17;69(34):9800-9812. Epub 2021 Aug 17.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.

Aging is the most common cause of several neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. The pathological hallmarks of age-dependent neuropathology consist of chronic neuroinflammation, oxidative stress, gliosis, learning disability, and cognitive decline. A novel hydrolyzed bioactive peptide mixture extracted from chicken meat, that is, hydrolyzed chicken extract (HCE) has been previously demonstrated to exert neuroprotective effects in rodents and humans. However, the mechanism of HCE on age-related neurological disorders remains unclear. Herein, we aimed to clarify the impact and mechanism of isolated bioactive components (BCs) from HCE on age-dependent neuroinflammation and cognitive impairment in middle-aged mice. We found that both BC and HCE supplementation ameliorated age-induced memory loss, alleviated hippocampal neuroinflammation and oxidative stress, followed by promoting hippocampal neurogenesis in mice. BC and HCE treatment also ameliorated age-dependent morphological anomalies and alleviated microgliosis and astrogliosis. In parallel, BC and HCE treatment showed a significant decrease in the NF-κB p65 and p38 MAPK signaling, which were associated with the enhancement of antioxidative enzymes activities. Furthermore, BC treatment attenuated the neuroinflammatory phenotypes by the decrease in M1-polarized microglia and the increase in M2-polarized microglia in vivo and in vitro. In addition, we found that cyclo(Phe-Phe), one of the cyclopeptides purified from BC, showed notable anti-inflammatory effects in BV2 cells. Taken together, BC might be used as a dietary supplement for alleviating age-dependent neuropathology in middle-aged individuals.
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http://dx.doi.org/10.1021/acs.jafc.1c03541DOI Listing
September 2021

Evaluation of the immunomodulatory effects of C9-13-CPs in macrophages.

Acta Biochim Biophys Sin (Shanghai) 2021 Aug;53(9):1154-1165

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China.

Short-chain chlorinated paraffins (SCCPs) have been listed as a new class of persistent organic pollutants by the Stockholm Convention. SCCPs exhibit carcinogenic-, endocrine-, and metabolism-disrupting effects. However, the knowledge of the immunomodulatory effects of SCCPs and their underlying mechanisms, especially in specific immune cells, remains limited. In addition to SCCPs, C9-13-CPs have also been detected in humans. In this study, murine RAW264.7 macrophages were exposed to C9-13-CPs at environmentally relevant concentrations to investigate whether or how C9-13-CPs exhibit immunomodulatory effects. The results showed that the exposure of RAW264.7 cells to C9-13-CPs increased cell viability, as assayed by MTT analysis at 490 nm, and also promoted cell proliferation, as indicated by EdU uptake assay, which was measured at excitation and emission wavelengths of 488 and 512 nm, respectively. In addition, exposure to C9-13-CPs not only led to elevated ATP level and intracellular Ca2+ level but also caused AMPK signaling activation and NF-κB signaling inhibition. Moreover, molecular docking showed that the β2-AR receptor could bind to C9-13-CPs. Taken together, these results suggest that the immune dysfunction of RAW264.7 cells caused by C9-13-CPs is closely related to the β2-AR/AMPK/NF-κB signaling axis.
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http://dx.doi.org/10.1093/abbs/gmab094DOI Listing
August 2021

Bisphenol A impairs cognitive function and 5-HT metabolism in adult male mice by modulating the microbiota-gut-brain axis.

Chemosphere 2021 Nov 26;282:130952. Epub 2021 May 26.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, China. Electronic address:

Bisphenol A (BPA) has been found to promote hepatotoxicity, reproductive toxicity, and developmental toxicity. However, the neurotoxicity and mechanism of BPA on cognitive function are still unclear. To that end, eight-week-old adult male and female C57BL/6J mice were exposed to 0.05, 0.5, 5, and 50 mg/kg BPA by dietary supplementation for 22 weeks. BPA exposure impaired learning and memory in male mice, associated with increased neuroinflammation and damaged blood-brain barrier. BPA exposure reduced the tight junctions in the colon, resulting in dysfunction of the gut barrier. The levels of neurotransmitters in the serum, hippocampus, and colon of male mice, including tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid, were all decreased by BPA, together with reduced expression of tryptophan and 5-HT metabolism-related genes. Cecal microbiota analysis revealed that the diversity and composition of the microbiota in male mice were markedly altered by BPA, leading to functional profile changes in the microbial community. These results suggest that the neurotoxicity of BPA in male mice may be partly regulated by the interactions of the microbiota-gut-brain axis. However, BPA has little effect on the cognitive function in female mice, which might be caused by the microbial differences and the role of estrogen receptors.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130952DOI Listing
November 2021

Developmental toxicity of procymidone to larval zebrafish based on physiological and transcriptomic analysis.

Comp Biochem Physiol C Toxicol Pharmacol 2021 Oct 15;248:109081. Epub 2021 May 15.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

As a broad-spectrum with low toxicity, procymidone (PCM), is widely used in agriculture and frequently observed in aquatic system, which may cause some impacts on aquatic organisms. Here, to determine the developmental toxicity of PCM, embryonic and larval zebrafish were exposed to PCM at 0, 1, 10, 100 μg/L in dehydrogenated natural water containing 0.01% acetone for 7 days. The results showed that high concentration of PCM could cause the pericardial edema and increase the heart rates in larval zebrafish, suggesting that PCM had developmental toxicity to zebrafish. We also observed that PCM exposure not only changed the physiological parameters including TBA, GLU and pyruvic acid, but also changed the transcriptional levels of glycolipid metabolism related genes. In addition, after transcriptomics analysis, a total of 1065 differentially expressed genes, including 456 up-regulated genes and 609 down-regulated genes, changed significantly in 100 μg/L PCM treated larval zebrafish. Interestingly, after GO (Gene Ontology) analysis, the different expression genes (DEGs) were mainly enriched to the three different biology processes including GABA-nervous, lipid Metabolism and response to drug. We also observed that the levels of GABA receptor related genes including gabrg2, gabbr1α, gabbr1 and gabra6α were inhibited by PCM exposure. Interestingly, the swimming distance of larval zebrafish had the tendency to decrease after PCM exposure, indicating that the nervous system was affected by PCM. Taken together, the results confirmed that the fungicide PCM could cause developmental toxicity by influencing the lipid metabolism and GABA mediated nervous system and behavior in larval zebrafish. We believed that the results could provide an important data for the influence of PCM on aquatic animals.
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http://dx.doi.org/10.1016/j.cbpc.2021.109081DOI Listing
October 2021

Isomer-Specific Effects of -9,-11- and -10,-12-CLA on Immune Regulation in Ruminal Epithelial Cells.

Animals (Basel) 2021 Apr 19;11(4). Epub 2021 Apr 19.

Institute of Food Sciences, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China.

In this study, we used transcriptomics and qPCR to investigate the potential immunoprotective effects of different conjugated linoleic acid (CLA) isomers, the natural rumen microbial metabolites, on lipopolysaccharide (LPS)-induced inflammation of ruminal epithelial cells (RECs) in vitro. The results showed that 100 μM -10,-12-CLA exerted higher anti-inflammatory effects than -9,-11-CLA by significantly downregulating the expression of genes related to inflammation, cell proliferation and migration in RECs upon LPS stimulation. Transcriptomic analyses further indicated that pretreatment with -10,-12-CLA, but not -9,-11-CLA, significantly suppressed the biological signals of GO terms' response to LPS, the regulation of signal transduction and cytokine production and KEGG pathways NF-κB, chemokine, NOD-like receptor, Hippo, PI3K-Akt, TGF-β and Rap1 signaling in RECs upon LPS stimulation. Furthermore, pretreatment with -10,-12-CLA significantly reduced the expression of lipogenic genes and the biosynthesis of the unsaturated fatty acid pathway in RECs compared with the LPS group, however, -9,-11-CLA exhibited the opposite results. These results suggest the distinct isomer differences of CLA in the regulation of inflammatory responses and adipocytokine signaling in RECs and will provide important references for determining their target use in the future.
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http://dx.doi.org/10.3390/ani11041169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072642PMC
April 2021

Neuroprotective effects of ProBeptigen/CMI-168 on aging-induced cognitive decline and neuroinflammation in mice: a comparison with essence of chicken.

Acta Biochim Biophys Sin (Shanghai) 2021 Mar;53(4):419-429

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.

Neuroinflammation and cognitive decline are the key pathological features in aging that bring detrimental impacts upon quality of life. However, there is no effective anti-aging pharmacological therapy thus far. Dietary supplements in particular essence of chicken (EC) has been found to be an effective remedy for alleviating mental stress and improving memory. In addition, a novel hydrolyzed chicken extract, ProBeptigen/CMI-168 (PB), showed beneficial effects on cognitive ability. However, the antiaging effect and possible mechanism of PB and EC are still unknown. Here, we investigated the antiaging effects of PB and EC on hippocampus-related cognitive decline and neuroinflammation in aged mice. PB and EC were administered for 16 weeks in 10-month-old mice. Both PB and EC treatments ameliorated age-related deterioration of learning and memory, and attenuated oxidative stress and inflammation in the hippocampus. These results were associated with decreased inflammatory cytokine levels and increased neurotransmitter levels in the hippocampus. The overall effects of improving aging-induced cognitive decline were more robust in PB-treated mice, while EC was effective in decreasing oxidative stress and inflammation. Moreover, alterations in the diversity and composition of the gut microbiota in aged mice were also regulated by both PB and EC, which induced distinguished features in the gut microbiota and their related functions. This study showed that PB exerts neuroprotective effects in aged mice, the mechanism of which might be different from that of EC. Therefore, PB has a potential as dietary supplement for ameliorating cognitive dysfunction and neuroinflammation in elderly individuals.
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http://dx.doi.org/10.1093/abbs/gmab009DOI Listing
March 2021

Preventive and Therapeutic Spermidine Treatment Attenuates Acute Colitis in Mice.

J Agric Food Chem 2021 Feb 4;69(6):1864-1876. Epub 2021 Feb 4.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.

Inflammatory bowel disease (IBD) is associated with acute and chronic inflammation of the gastrointestinal tract and has emerged to be a global disease. Spermidine, a natural polyamine, plays a critical role in maintaining cellular homeostasis. Herein, we investigated the impact and mechanism of spermidine on both dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced colitis in mice. We found that spermidine exerted protective effects against acute colitis, evidenced by reduced disease activity index (DAI) and colonic inflammation, increased colonic length, and upregulated tight junction proteins in these two colitis models. Importantly, spermidine exerted significant therapeutic and preventive effects against DSS-induced colitis. Pre- and post-treatment with spermidine reduced the expression of proinflammatory cytokines, phosphorylation of (nuclear factor-κB) NF-κB and (mitogen-activated protein kinase) MAPK, and the activation of F4/80 macrophages and T cells in the colon. Furthermore, spermidine upregulated M2 macrophage markers, whereas it downregulated M1 markers in the inflamed colons. In parallel, spermidine reduced M1 pro-inflammatory markers and enhanced M2 anti-inflammatory genes in RAW264.7 cells. These results revealed that spermidine-ameliorated colitis might be through the regulation of M1/M2 macrophage polarization. In addition, spermidine treatment also alleviated LPS/TNF-α-induced inflammation in Caco-2 cells. Taken together, spermidine prevented and reversed colonic inflammation in colitis mice and might be a promising candidate for IBD intervention.
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http://dx.doi.org/10.1021/acs.jafc.0c07095DOI Listing
February 2021

Polystyrene nanoparticles trigger the activation of p38 MAPK and apoptosis via inducing oxidative stress in zebrafish and macrophage cells.

Environ Pollut 2021 Jan 1;269:116075. Epub 2020 Dec 1.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, China. Electronic address:

Polystyrene nanoparticles (PS NPs), originated from breakdown of large plastic wastes, have already caused much concern for their environmental risks on health. This current study was aimed to reveal the toxicological mechanism of PS NPs on developing zebrafish and macrophage cells. To fulfill this purpose, 42 nm PS NPs were exposed to the early development stage of zebrafish for 5 days, the decreased heart rate and locomotor activity of zebrafish larvae were observed. The fluorescent PS NPs were used to precisely assess the accumulation of PS NPs in zebrafish larvae, and the results indicated that PS NPs not only accumulated in digestive system, but also infiltrated into the liver. More importantly, the transcriptomic analysis revealed that a total of 356 genes were differentially expressed and the KEGG class map showed significant differences in the MAPK pathway upon PS NPs treatment. Meanwhile, the induction of oxidative stress and inflammation were also observed in zebrafish larvae. Furthermore, PS NPs also induced oxidative damage and inflammatory response in RAW 264.7 cells, which activated p38 MAPK signal pathway and finally induced cell apoptosis. Our study provides a new understanding of MAPK signaling pathway involved in toxicity mechanism.
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http://dx.doi.org/10.1016/j.envpol.2020.116075DOI Listing
January 2021

Anti-diabetic effects of astaxanthin on an STZ-induced diabetic model in rats.

Endocr J 2021 Apr 2;68(4):451-459. Epub 2020 Dec 2.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, 310014, China.

Type 2 diabetes mellitus (T2DM), which is characterized by insulin resistance and relative insulin insufficiency, has become the most common chronic metabolic disease threatening global health. The preferred therapies for T2DM include lifestyle interventions and the use of anti-diabetic drugs. However, considering their adverse reactions, it is important to find a low-toxicity and effective functional food or drug for diabetes prevention and treatment. Astaxanthin is a potent antioxidant carotenoid found in marine organisms has been reported to prevent diet-induced insulin resistance and hepatic steatosis. To investigate the anti-diabetic effects of astaxanthin, male Wistar rats were fed a high-energy diet for 4 weeks, followed by a low dose streptozotocin (STZ) injection to induce the diabetes model, and the rats were then fed an astaxanthin-containing diet for another 3 weeks. Astaxanthin significantly decreased blood glucose and total cholesterol (TC) levels, and increased blood levels of high density lipoprotein cholesterol (HDL-C) in STZ-induced diabetic rats in a dose dependent manner. These results were associated with increased expression of insulin sensitivity related genes (adiponectin, adipoR1, and adipoR2) in vivo, thereby attenuating STZ-induced diabetes. In addition, we also compared the anti-diabetic effects of astaxanthin and monacolin K, which has been reported to downregulate hyperlipidemia and hyperglycemia. The results revealed that astaxanthin and monacolin K showed similar anti-diabetic effects in STZ-induced diabetic rats. Therefore, astaxanthin may be developed as an anti-diabetic agent in the future.
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http://dx.doi.org/10.1507/endocrj.EJ20-0699DOI Listing
April 2021

Transcriptomic Analyses Reveal the Protective Immune Regulation of Conjugated Linoleic Acids in Sheep Ruminal Epithelial Cells.

Front Physiol 2020 29;11:588082. Epub 2020 Oct 29.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China.

The ruminal epithelium is continuously challenged by antigens released by the lysis of dead microbial cells within the rumen. However, the innate immune system of the ruminal epithelium can almost always actively respond to these challenges. The cross talk between the ruminal microbiota and innate immune cells in the ruminal epithelium has been suggested to play an important role in sustaining the balance of immune tolerance and inflammatory response in the rumen. We hypothesized that conjugated linoleic acid (CLA), a functional microbial metabolite in the rumen, may contribute to the immune regulation in rumen epithelial cells (RECs); therefore, we first established an immortal REC line and then investigated the regulatory effects of CLA on the immune responses in these RECs. The results showed that long-term REC cultures were successfully established via SV40T-induced immortalization. Transcriptome analysis showed that a 100 μM CLA mixture consisting of 50:50 -9, -11:-10, -12 CLA significantly downregulated the expression of the inflammatory response-related genes TNF-α, IL-6, CX3CL1, IRF1, ICAM1 and EDN1, and upregulated the expression of the cell proliferation-related genes FGF7, FGF21, EREG, AREG and HBEGF and the lipid metabolism-related genes PLIN2, CPT1A, ANGPTL4, ABHD5 and SREBF1 in the RECs upon LPS stimulation. Correspondingly, the GO terms regulation of cell adhesion, response to stimulus and cytokine production and KEGG pathways TNF and HIF-1 signaling, ECM-receptor interaction and cell adhesion molecules were identified for the significantly downregulated genes, while the GO terms epithelial cell proliferation and regulation of epithelial cell migration and the KEGG pathways PPAR, ErbB and adipocytokine signaling were identified for the RECs with significantly upregulated CLA-pretreated genes upon LPS stimulation. These findings revealed that CLA conferred protective immunity onto the RECs by inhibiting proinflammatory processes, promoting cell proliferation and regulating lipid metabolism related to the immune response.
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http://dx.doi.org/10.3389/fphys.2020.588082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658390PMC
October 2020

Spermidine ameliorates high-fat diet-induced hepatic steatosis and adipose tissue inflammation in preexisting obese mice.

Life Sci 2021 Jan 10;265:118739. Epub 2020 Nov 10.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Aims: The therapeutic effects of spermidine on preexisting obese mice have been not fully elucidated. In this study, we assessed the anti-obesity impact of spermidine on high-fat diet (HFD)-induced obese mice.

Main Methods: C57BL/6J mice were fed a HFD for 16 weeks to induce obesity, and then treated with or without spermidine via drinking water for additional 8 weeks. The contributions of spermidine in regulating obesity phenotypes and metabolic syndrome were further evaluated.

Key Findings: Spermidine administration lowered fat mass and plasma lipid profile in HFD-induced obese mice without affecting body weight. In addition, spermidine attenuated hepatic steatosis by regulating lipid metabolism and enhancing antioxidant capacity. Moreover, spermidine reduced adipose tissue inflammation by decreasing inflammatory cytokine and chemokines expression, and these results might contributed to the enhanced thermogenic gene expression in brown adipose tissue. Furthermore, spermidine treatment enhanced gut barrier function by up-regulating tight junction- and mucin-related gene expression.

Significance: Spermidine-mediated protective impacts involve the regulation of lipid metabolism, inflammation response, gut barrier function and thermogenesis. These findings demonstrate that spermidine has potentials in treating obesity.
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http://dx.doi.org/10.1016/j.lfs.2020.118739DOI Listing
January 2021

Exposure to dibutyl phthalate impairs lipid metabolism and causes inflammation via disturbing microbiota-related gut-liver axis.

Acta Biochim Biophys Sin (Shanghai) 2020 Dec;52(12):1382-1393

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.

Dibutyl phthalate (DBP), a kind of typical environmental pollutant, is widely used as plasticizers, and its neurotoxicity and developmental toxicity have been found in recent years. However, whether oral DBP exposure will affect the homeostasis of gut microbiota and its adverse response in liver of mammalians remain unclear. In the present study, 10-week experimental cycles of vehicle or DBP (0.1 and 1 mg/kg) were given to 6-week-old C57BL/6J mice by oral gavage. Our results revealed that the body weight of mice was increased after exposure to both low and high doses of DBP. The serum levels of hepatic triglyceride and total cholesterol were significantly increased in response to both doses of DBP. In addition, some pivotal genes related to lipogenesis were also increased in liver at the mRNA level. Evaluation of gut microbiota by 16S rRNA sequencing technology showed that 0.1 mg/kg DBP exposure significantly affected gut microbiota at the phylum and genus levels. Moreover, DBP exposure decreased mucus secretion and caused inflammation in the gut, leading to the impairment of intestinal barrier function. Exposure to DBP inhibited the expression of peroxisome proliferator-activated receptor-γ and activated the expression of nuclear factor kappa B. In addition, DBP exposure increased the level of lipopolysaccharide in serum, and increased the expression of toll-like receptor 4 and the levels of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha, in the liver. These results indicated that exposure to DBP disturbed the homeostasis of gut microbiota, induced hepatic lipid metabolism disorder, and caused liver inflammation in mice via the related gut-liver axis signaling pathways.
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http://dx.doi.org/10.1093/abbs/gmaa128DOI Listing
December 2020

Spermidine improves gut barrier integrity and gut microbiota function in diet-induced obese mice.

Gut Microbes 2020 11;12(1):1-19

College of Biotechnology and Bioengineering, Zhejiang University of Technology , Hangzhou, China.

Obesity is associated with impaired intestinal barrier function and dysbiosis of the gut microbiota. Spermidine, a polyamine that acts as an autophagy inducer, has important benefits in patients with aging-associated diseases and metabolic dysfunction. However, the mechanism of spermidine on obesity remains unclear. Here, we show that spermidine intake is negatively correlated with obesity in both humans and mice. Spermidine supplementation causes a significant loss of weight and improves insulin resistance in diet-induced obese (DIO) mice. These effects are associated with the alleviation of metabolic endotoxemia and enhancement of intestinal barrier function, which might be mediated through autophagy pathway and TLR4-mediated microbial signaling transduction. Moreover, spermidine causes the significant alteration of microbiota composition and function. Microbiota depletion compromises function, while transplantation of spermidine-altered microbiota confers protection against obesity. These changes might partly be driven by an SCFA-producing bacterium, , which was decreased in obese subjects and subsequently increased by spermidine. Notably, the change of is significantly correlated with enhanced gut barrier function induced by spermidine. Our results indicate that spermidine supplementation may serve as a viable therapy for obesity.
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http://dx.doi.org/10.1080/19490976.2020.1832857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668533PMC
November 2020

Pharmacological activation of REV-ERBα improves nonalcoholic steatohepatitis by regulating intestinal permeability.

Metabolism 2021 01 21;114:154409. Epub 2020 Oct 21.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Background And Objectives: The gut-liver axis plays an important role in the pathogenesis of nonalcoholic steatohepatitis (NASH), and increased intestinal permeability causes transfer of endotoxin to the liver, which activates the immune response, ultimately leading to hepatic inflammation. Nuclear receptor Rev-erbα is a critical regulator of circadian rhythm, cellular metabolism, and inflammatory responses. However, the role and mechanism of Rev-erbα in gut barrier function and NASH remain unclear. In the present study, we investigated the involvement of Rev-erbα in the regulation of intestinal permeability and the treatment of NASH.

Methods And Results: The expression of tight junction-related genes and Rev-erbs decreased in the jejunum, ileum and colon of mice with high cholesterol, high fat diet (CL)-induced NASH. Chromatin immunoprecipitation analysis indicated that REV-ERBα directly bound to the promoters of tight junction genes to regulate intestinal permeability. Pharmacological activation of REV-ERBα by SR9009 protected against lipopolysaccharide-induced increased intestinal permeability both in vitro and in vivo, and these effects were associated with the activation of autophagy and decreased apoptotic signaling of epithelial cells. In addition, the chronopharmacological effects of SR9009 were more potent at Zeitgeber time 0 (ZT0) than at ZT12, which was contrary to the rhythm of Rev-erbs in the gastrointestinal tract. The administration of SR9009 attenuated hepatic lipid accumulation, insulin resistance, inflammation, and fibrosis in mice with CL diet-induced NASH, which might be partly attributed to the enhancement of intestinal barrier function.

Conclusion: Chronopharmacological activation of REV-ERBα might be a potential strategy to treat intestinal barrier dysfunction-related disorders and NASH.
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http://dx.doi.org/10.1016/j.metabol.2020.154409DOI Listing
January 2021

Crocin-I alleviates the depression-like behaviors probably via modulating "microbiota-gut-brain" axis in mice exposed to chronic restraint stress.

J Affect Disord 2020 11 18;276:476-486. Epub 2020 Jul 18.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, No. 6 District, Zhaohui, Hangzhou 310032, China. Electronic address:

Background: Depressive disorder is rapidly advancing in the worldwide, and therapeutic strategy through "gut-brain" axis has been proved to be effective. Crocin, has been found to have antidepressant activity. However, there is no thorough research for the effects of crocin-I (a major active component of crocin) on depression and its underlying mechanism.

Methods: We investigated the antidepressant effect of six-week oral administration of crocin-I in a mice model of depression induced by four-week CRS. Based on the "microbiota-gut-brain" axis, we determined the effects of crocin-I administration on gut microbiota, intestinal barrier function, short chain fatty acids and neurochemical indicators.

Results: Administration of crocin-I at a dose of 40 mg/kg for six weeks mitigated depression-like behaviors of depressed mice as evidenced by behaviors tests. In addition, crocin-I reduced the levels of lipopolysaccharide (LPS), Interleukin-6and tumor necrosis factor-α (TNF-α) in serum and TNF-α expression in the hippocampus, and increased the hippocampal brain-derived neurotrophic factor. Besides, 16 s rRNA sequencing revealed that crocin-I mitigated the gut microbiota dysbiosis in depressed mice as represented by the decreased abundance of Proteobacteria and Bacteroidetes, Sutterella spp. and Ruminococcus spp. and increased abundances of Firmicutes, Lactobacillus spp. and Bacteroides spp. Moreover, gas chromatography-mass spectrometry revealed that crocin-I reversed the decreased levels of short-chain fatty acids (SCFAs) in feces of depressed mice. Furthermore, crocin-I improved the impaired intestinal barrier by increasing expression of Occludin and Claudin-1, which contributed to the decreased LPS leakage.

Limitations: Only the male mice were used; the dose-effect relationship should be observed.

Conclusion: These results suggested that crocin-I effectively alleviated depression-like behavior, likely depended on the gut microbiota and its modulation of intestinal barrier and SCFAs.
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http://dx.doi.org/10.1016/j.jad.2020.07.041DOI Listing
November 2020

Maternal exposure to imazalil disrupts intestinal barrier and bile acids enterohepatic circulation tightly related IL-22 expression in F, F and F generations of mice.

J Hazard Mater 2021 02 9;403:123668. Epub 2020 Aug 9.

Department of Biotechnology, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China. Electronic address:

There is a growing body of evidence linking maternal exposure of environmental pollutants to intestinal and metabolic diseases that can be conserved across multiple generations. Here, female C57BL/6 mice were treated imazalil (IMZ) at dietary levels of 0, 0.025‰ and 0.25‰ during the gestation and lactation periods. The results demonstrated that IMZ treatment not only induced significant changes in the mucus secretion and ionic transport, but also disrupted the expression of antimicrobial peptides in the intestine of F, F and F generations. In addition, IMZ exposure altered BAs metabolism and the affected the expression levels of critical genes involved in BAs synthesis, signaling, transportation and apical uptake. The immune cell-produced cytokines were displaying extraordinary changes after IMZ exposure. In particular, whether it was in F0, F1-20d, F1-7 w or F2-20d, the expression of IL-22 had the trend of markedly increasing upon IMZ exposure. Correlation analyses revealed that the expression of IL-22 was positively correlated with the change of BAs metabolites. Together, all these results indicated that IMZ exposure was perceived as a major stress by the intestinal epithelium that strongly affected the intestinal barrier function (including mucus, CFTR, AMPs, inflammation), largely in response to an alteration of BAs metabolism.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123668DOI Listing
February 2021

Inhibitory effects of polystyrene microplastics on caudal fin regeneration in zebrafish larvae.

Environ Pollut 2020 Nov 26;266(Pt 3):114664. Epub 2020 Jul 26.

College of Environment, Zhejiang University of Technology, Hangzhou, 310032, PR China. Electronic address:

Microplastic pollution is pervasive in aquatic environments, but the potential effects of microplastics on aquatic organisms are still under debate. Given that tissue damage is unavoidable in fish and the available data mostly concentrate on healthy fish, there is a large chance that the ecotoxicological risk of microplastic pollution is underrated. Therefore, in this study, the effects of microplastics on the regenerative capacity of injured fish were investigated using a zebrafish caudal fin regeneration model. After fin amputation at 72 h post fertilization, the larvae were exposed to polystyrene microplastics (0.1-10 mg/L) with diameters of 50 or 500 nm. Microplastic exposure significantly inhibited fin regeneration, both morphologically and functionally. Furthermore, the signaling networks that regulate fin regeneration, as well as reactive oxygen species signaling and the immune response, both of which are essential for tissue repair and regeneration, were altered. Transcriptomic analyses of the regenerating fin confirmed that genes related to fin regeneration were transcriptionally modulated in response to microplastic exposure and that metabolic pathways were also extensively involved. In conclusion, this study demonstrated for the first time that microplastic exposure could disrupt the regenerative capacity of fish and might eventually impair their fitness in the wild.
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http://dx.doi.org/10.1016/j.envpol.2020.114664DOI Listing
November 2020

The Gut Microbiota and Its Metabolites, Novel Targets for Treating and Preventing Non-Alcoholic Fatty Liver Disease.

Mol Nutr Food Res 2020 09 10;64(17):e2000375. Epub 2020 Aug 10.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang, 310032, China.

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent metabolic disorders worldwide, along with obesity and type 2 diabetes. NAFLD involves a series of liver abnormalities from simple hepatic steatosis to non-alcoholic steatohepatitis, which can ultimately lead to liver cirrhosis and cancer. The gut-liver axis plays an important role in the development of NAFLD, which depends mainly on regulation of the gut microbiota and its bacterial products. These intestinal bacterial species and their metabolites, including bile acids, tryptophan catabolites, and branched-chain amino acids, regulate adipose tissue and intestinal homeostasis and contribute to the pathogenesis of NAFLD/non-alcoholic steatohepatitis. In this review, the current evidence regarding the key role of the gut microbiota and its metabolites in the pathogenesis and development of NAFLD is highlighted, and the advances in the progression and applied prospects of gut microbiota-targeted dietary and exercise therapies is also discussed.
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http://dx.doi.org/10.1002/mnfr.202000375DOI Listing
September 2020

β -Cypermethrin promotes the adipogenesis of 3T3-L1 cells via inducing autophagy and shaping an adipogenesis-friendly microenvironment.

Acta Biochim Biophys Sin (Shanghai) 2020 Aug;52(8):821-831

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.

The toxicity of synthetic pyrethroids has garnered attention, and studies have revealed that pyrethroids promote fat accumulation and lead to obesity in mice. Nevertheless, the effect of β-cypermethrin (β-CYP) on adipogenesis and its underlying mechanism remains largely unknown. In this study, mouse embryo fibroblasts 3T3-L1 cells were exposed to β-CYP, and the cell viability, intracellular reactive oxygen species (ROS) level, autophagy, and adipogenesis were assessed to investigate the roles of oxidative stress and autophagy in the toxic effects of β-CYP on adipogenesis. The results demonstrated that treatment with 100 μΜ β-CYP elevated the ROS level, decreased mitochondrion membrane potential, stimulated autophagy, and enhanced the adipogenesis induced by the mixture of insulin, dexamethasone, and 3-isobutyl-1-methylxanthine. However, co-treatment with N-acetyl-L-cysteine partially blocked the abovementioned effects of β-CYP in 3T3-L1 cells. In addition, co-treatment with rapamycin, an autophagy agonist, enhanced the inductive effect of β-CYP on adipogenesis, whereas co-treatment with 3-methyladenine blocked the enhancement of adipogenesis caused by β-CYP. Moreover, β-CYP also altered the microenvironment of 3T3-L1 cells to an adipogenesis-friendly one by reducing the extracellular expression of miR-34a, suggesting that the culture media of β-CYP-treated 3T3-L1 cells could shift macrophages to M2 type. Taken together, the data obtained in the present study demonstrated that β-CYP promoted adipogenesis via oxidative stress-mediated autophagy disturbance, and it caused macrophage M2 polarization via the alteration of miR-34a level in the microenvironment. The study demonstrated the adipogenesis-promoting effect of β-CYP and unveiled the potential mechanism.
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http://dx.doi.org/10.1093/abbs/gmaa049DOI Listing
August 2020

Sub-chronic carbendazim exposure induces hepatic glycolipid metabolism disorder accompanied by gut microbiota dysbiosis in adult zebrafish (Daino rerio).

Sci Total Environ 2020 Oct 9;739:140081. Epub 2020 Jun 9.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Carbendazim (CBZ) as a broad spectrum fungicide is widely used in the whole world to contorl plant diseases. With the application of CBZ in the agriculture, it has been detected in vegetables and fruits. Nowadays, it even has been detected in the watercourse and indoor dust. However, the toxic effects of CBZ on aquatic organisms have received limited attention. In this study, male adult zebrafish were exposed at 0, 30 and 100 μg/L CBZ for 21 days to assess its effects on hepatic glycolipid metabolism. After exposure, the body weight and length decreased, but the condition factor increased significantly. Some hepatic biochemical parameters including the levels of glucose, pyruvate, low density lipoprotein (LDL) and triglyceride (TG) decreased significantly in the liver of zebrafish after exposure with CBZ. Two transaminases alanine transaminase (ALT) and aspartate transaminase (AST) also increased significantly, indicating that subchronic CBZ exposure influenced the liver function. Moreover, the relative mRNA levels of some key genes related to the glycolysis and lipid metabolism in the liver also changed significantly. Furthermore, the transcriptome analysis showed that the carbon metabolism, lipid metabolism and detoxification metabolism were also affected in the liver of CBZ exposed zebrafish. Interestingly, we also found the amounts of the Firmicutes, Bacteroidetes, Actinobacteria, α-Proteobacteria, γ-Proteobacteria and Verrucomicrobia at phylum level significantly decreased in the gut. Sequencing V3-V4 region of 16S rRNA also demonstrated gut microbiota composition changed significantly according to weighted UniFrac distance analysis. Consequently, subchronic CBZ exposure induced hepatic metabolic disorder accompanied by gut microbiota dysbiosis in adult male zebrafish.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140081DOI Listing
October 2020

Exposure to low concentration of trifluoromethanesulfonic acid induces the disorders of liver lipid metabolism and gut microbiota in mice.

Chemosphere 2020 Nov 1;258:127255. Epub 2020 Jun 1.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, China. Electronic address:

Trifluoromethanesulfonic acid (TFMS) is the shortest chain perfluorinated compound. Recently, it has been identified as a persistent and mobile organic chemical with a maximum concentration of 1 μg/L in the environment. However, its toxicological mechanism remains unclear. In this study, to evaluate the liver and intestinal toxicity of TFMS in mammals, male mice were orally exposed to 0, 1, 10 and 100 μg/kg for 12 weeks. Our results showed that TFMS exposure reduced the epididymal fat weight in mice, caused the decrease of serum and liver triglyceride (TG) level and the increase of serum low density lipoprotein (LDL) level. Also, we observed the inflammatory cell infiltration in the liver of mice exposed to 10 μg/kg and 100 μg/kg TFMS, which was coupled with the increased mRNA expression levels of inflammatory factors such as COX2, TNF-α, IL-1β in the liver. In addition, the mRNA expression levels of lipid metabolism-related genes (PPAR-α, ACOX, SCD1, PPAR-γ, etc.) were significantly decreased in the liver of mice after exposure to both doses of TFMS. We also found TFMS exposure caused the imbalance of cecal gut microbiota and change of cecal microbiota diversity. KEGG pathway predictions showed that the exposure of 100 μg/kg TFMS changed the synthesis and degradation of ketone bodies, benzoate degradation and several other metabolic pathways. Our findings indicated that TFMS exposure disturbed the liver lipid metabolism possibly via altering the gut microbiota.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127255DOI Listing
November 2020

Pesticides-induced energy metabolic disorders.

Sci Total Environ 2020 Aug 28;729:139033. Epub 2020 Apr 28.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Metabolic disorders have become a heavy burden on society. Recently, through excessive use, pesticides have been found to be present in environmental matrixes and sometimes even accumulate in humans or other mammals through the food chain, which then causes health concerns. Evidence has indicated that pesticides have the potential to induce energy metabolic disorders by disturbing the physical process of energy absorption in the intestine and energy storage in the liver, adipose tissue and skeletal muscle in humans or other mammals. In addition, the homeostasis of energy regulation by the pancreas and immune cells is also affected by pesticides. These pesticide-induced disruptions ultimately cause abnormal levels of blood glucose and lipids, which in turn induce the development of related metabolic diseases, including overweight, underweight, insulin resistance and even diabetes. In this review, the results of previous studies focused on the induction of metabolic disorders by pesticides are summarized. We hope that this work will facilitate the discovery of a potential strategy for the treatment of diseases caused by pesticides.
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http://dx.doi.org/10.1016/j.scitotenv.2020.139033DOI Listing
August 2020

3-Methylcholanthrene alters the hepatic immune response in mice.

Acta Biochim Biophys Sin (Shanghai) 2020 05;52(5):570-572

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.

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http://dx.doi.org/10.1093/abbs/gmaa020DOI Listing
May 2020

Reprogramming Tumor Microenvironment with Photothermal Therapy.

Bioconjug Chem 2020 05 20;31(5):1268-1278. Epub 2020 Apr 20.

Department of Chemical and Biomolecular Engineering, National University of Singapore, 117585, Singapore.

The tumor microenvironment significantly influences cancer progression and therapeutic response. Reprogramming of tumor microenvironment has emerged as a strategy to assist conventional cancer treatment. In recent years, photothermal therapy has received considerable attention owing to its noninvasiveness, high temporal-spatial resolution, and minimal drug resistance. Apart from ablating cancer cells by generating heat upon light irradiation, photothermal therapy can also affect the tumor microenvironment, such as disrupting the tumor extracellular matrix and tumor vasculature. Moreover, cancer cell death by hyperthermia could potentially activate the immune system to fight against tumor. In this topical review, we focus on the recent progress of photothermal therapy based on tumor microenvironment remodeling, aiming to better guide the design of nanoparticles for cancer photoimmunotherapy.
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http://dx.doi.org/10.1021/acs.bioconjchem.0c00135DOI Listing
May 2020

β-Cypermethrin Alleviated the Inhibitory Effect of Medium from RAW 264.7 Cells on 3T3-L1 Cell Maturation into Adipocytes.

Lipids 2020 05 31;55(3):251-260. Epub 2020 Mar 31.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang, 310032, China.

Studies have elucidated that pyrethroids induce adipogenesis. It is also known that macrophages can affect the homeostasis of adipose tissue. However, whether and how the β-cypermethrin (β-CYP)-mediated inhibition of the macrophages affects adipogenesis remain unknown. To explore the effects of β-CYP on adipogenesis through modulating the function of macrophages, 3T3-L1 cells, a preadipocyte cell line, were exposed to culture medium from either RAW 264.7 cells, a macrophage cell line (RM), or β-CYP-treated RAW 264.7 cells (CRM). CRM decreased the inhibitory effects of RM treatment on cell proliferation and adipogenesis, as lipid accumulation, the CEBPA content, and Fasn and Acaca expression in 3T3-L1 cells were higher following CRM treatment than following RM treatment through the higher levels of the demethylated CEBPA promoter in 3T3-L1 cells. However, the medium from β-CYP- and N-acetyl-L-cysteine-cotreated RAW 264.7 cells (CNRM) partially restored the inhibitory effects of RAW 264.7 cells on 3T3-L1 cells that had been reduced by CRM, indicating that β-CYP might reduce the cytotoxicity and inhibitory effects of RAW 264.7 cells on the adipogenesis of 3T3-L1 cells through elevating ROS levels in RAW 264.7 cells. Moreover, exposure to β-CYP downregulated the TNF-α secretion in RAW 264.7 cells. In conclusion, these data demonstrated that β-CYP affected the function of RAW 264.7 cells, alleviating their inhibitory effects on adipogenesis and CEBPA demethylation in 3T3-L1 cells. β-CYP might achieve these effects through downregulating the secretion of TNF-α via elevating ROS levels in RAW 264.7 cells. Our experiments provide a new perspective on the obesogenic effect of pyrethroids.
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http://dx.doi.org/10.1002/lipd.12234DOI Listing
May 2020

Depression-like behaviors are accompanied by disrupted mitochondrial energy metabolism in chronic corticosterone-induced mice.

J Steroid Biochem Mol Biol 2020 06 8;200:105607. Epub 2020 Feb 8.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, China. Electronic address:

Stress exerts its negative effects by interference with mitochondrial energy production in rodents, and is able to impair mitochondrial bioenergetics. However, the underlying mechanism that stress hormone impacts depression-like behaviors and mitochondrial energy metabolism is still not well understood. Here, we investigated the changes of depression-like behaviors and mitochondrial energy metabolism induced by chronic corticosterone (CORT). The results showed that after treatment with CORT for 6 weeks, mice displayed depression-like behaviors, which were identified by tail suspension test, forced swimming test and open field test. Then, the livers were isolated and tested by RNA sequencing and metabolome analysis. RNA sequencing showed 354 up-regulated genes and 284 down-regulated genes, and metabolome analysis revealed 280 metabolites with increased abundances and 193 metabolites with reduced abundances in the liver of mice after CORT, which were closely associated with lipid metabolism and oxidative phosphorylation in mitochondria. Based on these findings, the changes of mitochondrial energy metabolism were investigated, and we revealed that CORT condition inhibited glycolysis and fatty acid degradation pathway, and activated synthesis of triacylglycerol, leading to the reduced levels of acetyl-CoA and attenuated TCA cycle. Also, the pathways of NAD synthesis were inhibited, resulting in the reduced activity of sirtuin 3 (SIRT3). Thus, all of these observations disrupted the function of mitochondria, and led to the decrease of ATP production. Our findings uncover a novel mechanism of stress on depression-like behaviors and mitochondrial energy metabolism in rodents.
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http://dx.doi.org/10.1016/j.jsbmb.2020.105607DOI Listing
June 2020

Polystyrene microplastic exposure disturbs hepatic glycolipid metabolism at the physiological, biochemical, and transcriptomic levels in adult zebrafish.

Sci Total Environ 2020 Mar 27;710:136279. Epub 2019 Dec 27.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Microplastics (MPs), which are new types of environmental pollutants, have recently received widespread attention worldwide. MPs can accumulate in the bodies of animals and in plants, and they can also enter the human body through the food chain. However, knowledge of the effects of MPs on the health of animals is still limited. In this experiment, adult male zebrafish were exposed to 20 or 100 μg/L of 5 μm polystyrene MP for 21 days in an attempt to determine the hepatic effects related to glycolipid metabolism at the biochemical and transcriptomic levels. It was found that body weight and condition factor decreased significantly in zebrafish after exposure to 20 and 100 μg/L polystyrene MP for 21 days. The transcription levels of major genes related to glycolipid metabolism decreased significantly in the liver. Correspondingly, the levels of major biochemical parameters, including Glu, pyruvic acid, α-ketoglutaric acid and IDH, were also decreased in the livers of exposed zebrafish, especially those in the 100 μg/L polystyrene MP-treated group. Moreover, the data on the hepatic transcriptome also confirmed that some genes related to fatty acid metabolism, amino acid metabolism and carbon metabolism tended to be decreased in the livers of exposed zebrafish. Taken together, our data confirmed that polystyrene PS-MP can induce hepatic glycolipid metabolism disorder at the physiological, biochemical, and transcriptomic levels in adult zebrafish after 21 days of exposure.
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http://dx.doi.org/10.1016/j.scitotenv.2019.136279DOI Listing
March 2020

Adipose Tissue Macrophage Phenotypes and Characteristics: The Key to Insulin Resistance in Obesity and Metabolic Disorders.

Obesity (Silver Spring) 2020 02 5;28(2):225-234. Epub 2020 Jan 5.

Division of Metabolism and Biosystemic Science, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.

Obesity is one of the most serious global health problems, with an incidence that increases yearly and coincides with the development of a variety of associated comorbidities (e.g., type 2 diabetes, nonalcoholic fatty liver disease, some immune-related disorders). Although many studies have investigated the pathogenesis of overweight and obesity, multiple regulatory factors underlying the onset of obesity-related metabolic disorders remain elusive. Macrophages contribute to modulation of obesity-related inflammation and insulin resistance (IR); adipose tissue macrophages are particularly important in this context. Based on newly identified links between the chemokine system and obesity, macrophage polarization has become an essential target of new therapies for obesity-related IR. The findings of multiple studies imply that variations in gut microbiota and its metabolites might contribute to the regulation of obesity and related metabolic disorders. Recently, several novel antidiabetic drugs, applied as treatment for weight loss, were shown to be effective for obesity-induced IR and other comorbidities. The present review will discuss the properties and functions of macrophages in adipose tissue under conditions of obesity from three perspectives: the chemokine system, the gut microbiota, and antidiabetic drug application. It is proposed that macrophages might be a key therapeutic target for obesity-induced complications.
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http://dx.doi.org/10.1002/oby.22674DOI Listing
February 2020
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